Tolmachev Vladimir, Stone-Elander Sharon
Division of Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University, SE-75181 Uppsala, Sweden.
Biochim Biophys Acta. 2010 May;1800(5):487-510. doi: 10.1016/j.bbagen.2010.02.002. Epub 2010 Feb 11.
Dynamic biomedical research is currently yielding a wealth of information about disease-associated molecular alterations on cell surfaces and in the extracellular space. The ability to visualize and quantify these alterations in vivo could provide important diagnostic information and be used to guide individually-optimized therapy. Biotechnology can provide proteinaceous molecular probes with highly specific target recognitions. Suitably labelled, these may be used as tracers for radionuclide-based imaging of molecular disease signatures. If the labels are positron-emitting radionuclides, the superior resolution, sensitivity and quantification capability of positron emission tomography (PET) can be exploited.
This article discusses different approaches to labelling proteins with positron-emitting nuclides with suggestions made depending on the biological features of the tracers.
Factors such as matching biological and physical half-lives, availability of the nuclide, labelling yields, and influences of labelling on targeting properties (affinity, charge and lipophilicity, cellular processing and retention of catabolites) should be considered when selecting a labelling strategy for each proteinaceous tracer.
The labelling strategy used can make all the difference between success and failure in a tracer application. This review emphasises chemical, biological and pharmacological considerations in labelling proteins with positron-emitting radionuclides.
动态生物医学研究目前正在产生大量有关细胞表面和细胞外空间中与疾病相关的分子改变的信息。在体内可视化和量化这些改变的能力可以提供重要的诊断信息，并用于指导个体化优化治疗。生物技术可以提供具有高度特异性靶点识别能力的蛋白质分子探针。经过适当标记后，这些探针可作为基于放射性核素的分子疾病特征成像的示踪剂。如果标记物是发射正电子的放射性核素，则可以利用正电子发射断层扫描（PET）的高分辨率、高灵敏度和定量能力。
本文讨论了用发射正电子的核素标记蛋白质的不同方法，并根据示踪剂的生物学特性提出了建议。
在为每种蛋白质示踪剂选择标记策略时，应考虑生物半衰期和物理半衰期的匹配、核素的可获得性、标记产率以及标记对靶向特性（亲和力、电荷和亲脂性、细胞处理和代谢产物保留）的影响等因素。
所采用的标记策略可能决定示踪剂应用的成败。本综述强调了在用发射正电子的放射性核素标记蛋白质时的化学、生物学和药理学考虑因素。
